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PubMed1993

The European Organization for Research and Treatment of Cancer. Approach to quality of life assessment: guidelines for developing questionnaire modules. EORTC Study Group on Quality of Life.

The EORTC Study Group on Quality of Life (the Study Group) has adopted a modular approach to quality of life (QOL) assessment in cancer clinical trials. A 'core' instrument-the QLQ-C30-has been designed to cover a range of QOL issues relevant to a broad spectrum of cancer patients. It is intended that this QLQ-C30 be supplemented by more specific subscales ('modules') to assess aspects of QOL of particular importance to specific subgroups of patients. Since individual members of the Study Group were to be involved in module development, guidelines were required to standardize the module development process in order to ensure uniformly high quality across modules. These guidelines are presented in this paper. The term 'module' is defined, the composition of modules is outlined, and the criteria used to develop modules are specified. The module development process, consisting of four phases (generation of relevant QOL issues, operationalization of the QOL issues into a set of items, pretesting the module questionnaire, and large-scale field-testing) is described in detail. Further, issues related to cross-cultural instrument development, and the need for monitoring the module development process from within the Study Group are discussed. Finally, experiences with developing two site-specific modules (i.e., for head and neck, and breast cancer), are presented and the extent to which the guidelines meet practical requirements is discussed. The guidelines appear to provide a practical tool for module construction, that can facilitate the development of a comprehensive system for assessing the QOL of cancer patients internationally.

Breast Neoplasms↗
PubMed2005

Negative GABA(A) modulators attenuate the discriminative stimulus effects of benzodiazepines and the neuroactive steroid pregnanolone in rhesus monkeys.

RATIONALE: Negative GABA(A) modulators (i.e., inverse agonists) might be useful for identifying mechanisms at the GABA(A) receptor complex that mediate the effects of positive GABA(A) modulators, especially those for which there are no available competitive antagonists. OBJECTIVE: Drug discrimination was used to examine antagonism of a 5-beta neuroactive steroid (pregnanolone) and a benzodiazepine (midazolam) by several negative GABA(A) modulators in rhesus monkeys. METHODS: One group of monkeys (n=5) received 5.6 mg kg(-1) day(-1) of diazepam (p.o.) and discriminated the benzodiazepine antagonist flumazenil (0.1 or 0.32 mg/kg s.c.); another group of monkeys (n=5) discriminated the benzodiazepine midazolam (0.32 mg/kg s.c.). RESULTS: In diazepam-treated monkeys, negative GABA(A) modulators with increasing efficacy, including Ro 15-4513, ethyl beta-carboline-3-carboxylate (beta-CCE), methyl beta-carboline-3-carboxylate (beta-CCM) and methyl-6,7-dimethoxyl-4-ethyl-beta-carboline-3-carboxylate (DMCM), substituted for flumazenil. In monkeys discriminating midazolam, pregnanolone occasioned high levels of midazolam-lever responding, and these effects were attenuated by beta-CCE and beta-CCM, but not by flumazenil, Ro 15-4513, or DMCM. The midazolam discriminative stimulus also was attenuated by beta-CCM and DMCM; Schild analysis was consistent with a simple competitive interaction between midazolam and beta-CCM but not between midazolam and DMCM. CONCLUSIONS: Negative modulators are qualitatively similar to neutral modulators in diazepam-treated animals; however, interactions between negative modulators and midazolam suggest that different receptors mediate the effects of some (DMCM) and not other (beta-CCM) negative modulators. Negative modulators at benzodiazepine sites exert efficacy-dependent antagonism of positive modulators at neuroactive steroid sites. Without competitive antagonists at neuroactive steroid or barbiturate sites, negative modulators could prove useful for examining the mechanism of action of different classes of positive GABA(A) modulator.

Animals↗
PubMed1993

Encoding of amplitude-modulated tones by neurons of the inferior colliculus of the kitten.

Responses of single neurons of the central nucleus of the inferior colliculus (ICC) of kittens 4-43 days of age were studied using sinusoidally amplitude-modulated (AM) tones delivered monaurally or binaurally via sealed and calibrated earphones. The carrier frequency of the AM signal was set to the CF of the neuron. CFs ranged from 2-26 kHz. During the about first 2 weeks of postnatal life, ICC neurons responded to sound with periodic bursts of activity. In response to AM tones, discharges of ICC neurons at all ages studied were phase-locked to the envelope of the modulation waveform over a wide range of stimulus level and modulation depth. A linear relationship, independent of SPL, was found between the average phase of discharge on the modulation cycle and modulation frequency. The slope of the line represents a time delay, which was highly correlated with the first-spike latency to tone onset, and hence with the age of the animal. The mean effective phase of the discharge remained relatively constant with age. There was little systematic change in average phase of discharge with changing stimulus level or modulation depth, although the number of spikes evoked and the temporal pattern of the spikes within a modulation cycle could vary. The sensitivity function relating spike synchrony or spike count to modulation frequency was typically band-pass in nature. The most effective modulation frequency (MEMF) was, on average, 15 Hz, far below that reported for adult cat ICC cells. When AM tones were delivered binaurally, the discharge was a periodic function of the interaural phase difference of the stimulus envelopes. The results indicate that prior to the time the cochlea is able to respond to most environmental sounds, monaural and binaural circuits involving the ICC faithfully transmit information pertaining to amplitude-modulated signals in the rate and timing of their discharges. During the next several weeks, when neural thresholds fall to adult levels, ICC circuits are activated by amplitude modulated sounds at levels encountered in the normal acoustic environment even though they are restricted to modulation frequencies below those encoded by the adult.

Acoustic Stimulation↗
PubMedDate not supplied

Pulse modulation detection in human motion vision.

We present data on the human sensitivity to temporal pulse modulations of target velocity. We measured threshold detection modulation amplitudes for pulse-shaped speed modulations, as a function of pulse duration and temporal frequency. At short pulse durations (up to 50 msec) and low modulation frequency (1 Hz), detection amplitudes are ruled by Bloch's law: the product of pulse duration and threshold modulation amplitude is a constant. This constant corresponds to a position modulation with an amplitude of 3 arc min in a coordinate frame that moves at the average speed (3 deg/sec) of the target. At longer pulse durations we find deviations from Bloch's law. Speed modulation thresholds are not critically dependent on target luminance contrast. These results are modeled by a modulation detection process in two stages. A functional description of the first stage is filtering of the true speed modulation signal by a second order low-pass filter with a characteristic time constant of 20-25 msec. The second (decision) stage is variance detection: modulations are detected when the variance of the filtered modulation function exceeds a certain threshold variance. The square-root threshold variance is estimated 8-10%. This two-parameter model accurately predicts the measured dependence of pulse modulation detection thresholds on pulse duration and pulse density.

Filtration↗
PubMed1987

Stimulus properties influencing the responses of inferior colliculus neurons to amplitude-modulated sounds.

The temporal pattern of the responses of neurons in the inferior colliculus of the anesthetized rat were studied using continuous tone or noise carrier signals, amplitude modulated by pseudorandom noise. Period histograms of the responses, cross-correlated with the pseudorandom noise, gave an estimate of the unit's impulse responses to modulation. The amplitude-modulation rate transfer function (MTF) was obtained by Fourier transforming the correlograms. At sound levels within approximately 15 dB of the unit threshold, the MTFs were near lowpass functions between 6 and 200 Hz but became more bandpass-like as the intensity was increased. There was a steep decline in the response to modulation at modulation frequencies above 200 Hz for all stimulus intensities. For the bandpass-type MTFs the greatest modulation of the discharge pattern occurred at modulation frequencies between 10 and 200 Hz with a maximum in the distribution of MTF peak values between 100 and 120 Hz. There was no consistent relationship with characteristic frequency of either the position of the MTF peak or the high-frequency cutoff of the MTF. The cross-correlograms obtained at high stimulus intensities (30-60 dB above threshold) often showed a negative peak, representing a decrease in the probability of firing in response to intensity increments in the stimulus, and denoting a nonmonotonic rate-intensity function. The MTFs for units responding to amplitude-modulated broadband noise were often flatter in the low frequency region than those generated with tone carriers at corresponding intensities. For some units addition of a broadband noise background to the modulated tone changed the response characteristic of the MTF from bandpass to lowpass and shifted the MTF peak to a lower modulation frequency. The results demonstrate that although neurons in the inferior colliculus are selectively sensitive to the modulation frequency of dynamic stimuli, the response characteristics are not invariant, but instead are closely dependent on the conditions under which the modulation is presented.

Acoustic Stimulation↗
PubMed1993

Secondary structure of a pair of fibronectin type 1 modules by two-dimensional nuclear magnetic resonance.

The fourth and fifth type 1 module pair, corresponding to residues 151-244 from the amino terminus of human fibronectin, has been produced as a recombinant protein using a yeast expression system and studied by two-dimensional homonuclear 1H nuclear magnetic resonance (NMR) spectroscopy. The sequence-specific resonance assignment of the 1H NMR spectrum has been completed using a combination of 2D 1H nuclear Overhauser effect (NOE) spectroscopy, homonuclear Hartmann-Hahn, and correlated spectroscopy spectra recorded under a variety of pH and temperature conditions. Slow exchanging amide protons have been identified and estimates of many backbone 3JNH-C alpha H coupling constants were obtained by line shape fitting. The secondary structures of each module conform closely to the "consensus" fibronectin type 1 module structure determined previously for two other single type 1 modules. In the module pair described here, the two modules are linked by a short five-residue linker which appears to form a turn. The intermodule interface is defined by NOEs observed between a hydrophobic three-residue sequence from the fourth type 1 module and residues in the first double-stranded beta-sheet of the fifth type 1 module. The interaction is dominated by a tryptophan residue (unconserved in other type 1 sequences) within the fourth module, which causes large upfield ring current shifts for several proton resonances from the beta-sheet of the fifth module. The NMR data indicate that there is little or no relative reorientation of the two modules about the linker region but rather that the two modules combine with a fixed and intimate hydrophobic contact.

Amino Acid Sequence↗
PubMed1973

Regulation of nucleoside cyclic 3':5'-monophosphate phosphodiesterase activity from rat brain by a modulator and Ca2+.

Gel filtration of the 40,000 rpm supernatant fraction of a homogenate of rat cerebral cortex on a Sepharose 6B column yielded two fractions: fraction II with the "Ca(2+) plus Mg(2+)-dependent" phosphodiesterase activity and fraction III containing its modulator. The activity of fraction II was stimulated by micromolar concentrations of Ca(2+) and the modulator when present together; the modulator stimulated the activity of fraction II only when the Ca(2+) concentration was above a threshold value (about 2 muM with 0.4-1 muM substrate), and the stimulatory effect of Ca(2+) was dependent upon the presence of the modulator. A possibility is discussed that the modulator may reversibly bind to the enzyme, which by itself is inactive, to form an active enzyme-modulator complex and that Ca(2+) stimulates the activity of phosphodiesterase by shifting the equilibrium between these three species towards the formation of the active enzyme-modulator complex. Although fraction II hydrolyzed both cyclic AMP and cyclic GMP, hydrolysis of the latter was more significantly influenced by Ca(2+) and the modulator than that of the former, and the "Ca(2+) plus Mg(2+)-dependent" phosphodiesterase is likely to be a cyclic GMP enzyme. This conclusion is based on the following evidence: (a) Ca(2+) stimulated hydrolysis of cyclic GMP by fraction II more than that of cyclic AMP. (b) In the presence of Ca(2+) and the modulator, fraction II hydrolyzed cyclic GMP about 8 times faster than cyclic AMP when incubated with 0.4 muM substrate. (c) Half-maximal stimulation of hydrolysis of cyclic GMP was attained at a lower concentration of Ca(2+) (4 muM) than that of cAMP (8 muM). (d) Increase in the concentration of Ca(2+) from 0.06 muM to 12 muM in the presence of the modulator caused a decrease in the K(m) value of cyclic GMP hydrolysis by fraction II from 20 muM to 2 muM accompanied by 4-fold increase in the V(max) value. Under similar conditions, there was only a slight decrease in the K(m) value of cylic AMP hydrolysis (90 muM --> 50 muM), although the V(max) value increased 7-fold. The anomalous shape of the kinetic plot of cyclic GMP hydrolysis became linear when the Ca(2+) concentration was increased in the presence of the modulator. The modulator seems to be a protein, but it is heat stable. It is probably identical to the protein activator of phosphodiesterase first described by Cheung.

Animals↗
PubMed1996

Non-modulating hypertension: evidence for the involvement of kallikrein/kinin activity associated with overactivity of the renin-angiotensin system. Successful blood pressure control during long-term Na+ restriction.

BACKGROUND: Non-modulating hypertensives are a subset of sodium-sensitive hypertensives characterized by a failure to modulate renal, vascular and adrenal glomerulosa responsivenesses to angiotensin II appropriately. OBJECTIVE: To investigate the plasma renin activity (PRA) and urinary kallikrein-like activity (Ku) under different sodium conditions in essential hypertensive patients and in the modulating and non-modulating subsets of hypertensives. Additionally, in these groups of patients, the effects on blood pressure of a sustained Na+ restriction were evaluated. METHODS: Fifteen normotensives (10 men, aged 29 +/- 5 years) and 54 untreated hypertensives (30 men, aged 34 +/- 7 years) were each administered subsequently three different diets containing 240, 140 and 50 mmol/day Na+, each diet for 10 days. At the end of each period, the PRA, Ku, 24 h urinary volume and urinary Na+ excretion were measured. Afterwards, the essential hypertensives were classified as 29 modulating essential hypertensives (MHT, 20 men, aged 32 +/- 7 years) and 25 non-modulating essential hypertensives (NMHT, 10 men, aged 36 +/- 8 years). Non-modulating ones were identified as individuals who failed to increase their effective renal plasma flow and to decrease their filtration fraction by at least 30% from baseline values, 10 days after changing from a low (10 mmol/day) to a high (260 mmol/day) Na+ intake. Blood pressure was measured with a Dinamap 8100 Critikon device. Both PRA and Ku were measured during normal Na+ intake by standard methods. Patients were administered a low-Na+ diet (10-50 mmol/day) for 12 months. RESULTS: In essential hypertensives, Ku was lower under the three Na+ diets than it was in normotensives (P < 0.01) whereas the PRA was higher in hypertensives only during the low Na+ intake (P < 0.01). The non-modulating patients showed significantly higher PRA levels (4.0 +/- 0.8 ng ml h, P < 0.05) than did modulating ones (2.6 +/- 1.0 ng ml h) or normotensives (2.3 +/- 1.0 ng ml h). Conversely, non-modulating hypertensives had lower Ku (4.1 +/- 1.0 IU/24 h, P < 0.025) than did modulating ones (6.2 +/- 1.0 IU/24 h) or normotensives (7.8 +/- 2.0 IU/24 h). Blood pressure was significantly reduced during low Na+ intake only in normotensives (month 6: 143 +/- 4/94 +/- 2 mmHg; month 12: 139 +/- 5/89 +/- 3 mmHg) compared with baseline values (169 +/- 4/102 +/- 6 mmHg, P < 0.025). CONCLUSIONS: It was shown that, in non-modulating hypertensives, in addition to an increased PRA, a reduced kallikrein-like activity coexists and seems to be associated with the impaired Na+ handling. Moreover, in these untreated patients the Na+ restriction was able to exert an antihypertensive effect even for long periods.

Adult↗
PubMed2005

Encoding frequency modulation to improve cochlear implant performance in noise.

Different from traditional Fourier analysis, a signal can be decomposed into amplitude and frequency modulation components. The speech processing strategy in most modern cochlear implants only extracts and encodes amplitude modulation in a limited number of frequency bands. While amplitude modulation encoding has allowed cochlear implant users to achieve good speech recognition in quiet, their performance in noise is severely compromised. Here, we propose a novel speech processing strategy that encodes both amplitude and frequency modulations in order to improve cochlear implant performance in noise. By removing the center frequency from the subband signals and additionally limiting the frequency modulation's range and rate, the present strategy transforms the fast-varying temporal fine structure into a slowly varying frequency modulation signal. As a first step, we evaluated the potential contribution of additional frequency modulation to speech recognition in noise via acoustic simulations of the cochlear implant. We found that while amplitude modulation from a limited number of spectral bands is sufficient to support speech recognition in quiet, frequency modulation is needed to support speech recognition in noise. In particular, improvement by as much as 71 percentage points was observed for sentence recognition in the presence of a competing voice. The present result strongly suggests that frequency modulation be extracted and encoded to improve cochlear implant performance in realistic listening situations. We have proposed several implementation methods to stimulate further investigation. Index Terms-Amplitude modulation, cochlear implant, fine structure, frequency modulation, signal processing, speech recognition, temporal envelope.

Algorithms↗
PubMed2006

NMR structure of the first Ig module of mouse FGFR1.

Fibroblast growth factor (FGF) receptors (FGFRs) regulate a multitude of cellular processes during embryogenesis and in the adult. The extracellular part of the prototypical FGFR consists of three Ig modules (Ig1 - Ig3), in which Ig2 and Ig3 determine affinity and specificity for FGF and heparin, while the Ig1 module is thought to have a regulatory function. The crystal structures of the Ig2 and Ig3 modules alone and in complex with FGF have previously been reported. The structure of the Ig1 module is unknown, and very little is known about the structural determinants for the regulatory function of this module. We describe here the NMR structure of the Ig1 module of mouse FGFR1. The three-dimensional fold of the module belongs to the intermediate Ig subgroup and can be described as a beta-barrel consisting of two beta-sheets. One sheet is formed by A', G, F, C, and C', and the other by A, B, B', E, and D beta-strands. The overall strand topology of the Ig1 module is similar to that of the Ig2 and Ig3 modules. However, the A/A' loop of the Ig1 module is much longer than that of the Ig2 and Ig3 modules. It contains eight extra residues compared to the Ig3 module, and five extra residues compared to Ig2.

Animals↗
PubMedDate not supplied

Variable versus fixed modulation of proton beams for treatments in the cranium.

Dose distributions in the cranium with fixed and with variably modulated proton beams were compared. The variable modulation was designed to tailor the proximal high-dose region of each field to the target volume surface whereas the fixed modulation beams had a constant modulation determined by the greatest extent of the target. Dose-volume histograms of normal tissues were compared, as were the estimated complication probabilities. Twelve patients with chordomas or chondrosarcomas of the base of skull who had been treated to approximately 70 cobalt Gray equivalent (CGE) were evaluated. Dose distributions of the actual treatments were compared to those which would have been delivered had the proton beams been variably modulated; two patients for whom x-ray plans were available were also evaluated. The greatest difference in dose between the variable and fixed modulation proton beams, averaged over all the patients, was 13.8 CGE (8.0-18.0 CGE range). Much of this reduction occurred in the brain, particularly the temporal lobes. In those temporal lobes receiving significant doses, variable modulation reduced the volume receiving more than 54 CGE by 3.0 cc; all temporal lobes had at least a 5 CGE difference to some portion, half had more than 10 CGE and three more than 15 CGE difference to some portion. The optic structures, brainstem and spinal cord received from 1 to 3 CGE less dose with the variability modulated beams. Eight of the parotid glands received more than 20 CGE to more than half their volume with the fixed modulation beams; in these, variable modulation reduced the mean dose by 5.3 CGE. The reduction in integral dose with variable as compared to fixed modulation was in the range 3 to 12%; this gain was considerably less than the gain for uniformly modulated proton beams over x-rays in the two patients for whom x-ray plans were available.

Brain Stem↗
PubMed1983

Time course of adaptation and recovery of channels selectively sensitive to frequency and amplitude modulation.

In a series of experiments we investigated the time course of adaptation and recovery of channels in the human auditory system selectively sensitive to frequency and amplitude modulation (FM and AM). We determined the rate of loss of sensitivity to modulation using sinusoidal frequency or amplitude modulation (SFM or SAM) of a 50 dB SL, 500-Hz pure tone carrier over a 30-min period. Adaptation stimuli were modulated at ten times the preadaptation modulation detection threshold, as determined immediately before the 30-min adaptation session. Modulation rates investigated were 2, 4, 8, 16, and 32 Hz. Long exposure to SFM always elevated thresholds for detection of SFM more than this exposure elevated thresholds for detection of SAM. Similarly, adapting to SAM always elevated SAM detection thresholds more than SFM thresholds. Loss of sensitivity during adaptation was relatively slow; asymptotic loss of modulation sensitivity took 20 to 30 min. The recovery of modulation sensitivity after cessation of the modulation component of the adapting stimulus was determined in a second experiment. Recovery was found to be rapid; most of the recovery occurred within the first 60 sec. Our evidence suggests that there exist two types of modulation-sensitive channels in the human auditory system--one selectively sensitive to amplitude modulation and the other to frequency modulation. They appear to have similar time courses for adaptation and for recovery.

Adaptation, Physiological↗
PubMed1989

Neuronal responses to amplitude-modulated and pure-tone stimuli in the guinea pig inferior colliculus, and their modification by broadband noise.

Neuronal responses were recorded to pure and to sinusoidally amplitude-modulated (AM) tones at the characteristic frequency (CF) in the central nucleus of the inferior colliculus of anesthetized guinea pigs. Temporal (synchronized) and mean-rate measures were derived from period histograms locked to the stimulus modulation waveform to characterize the modulation response. For stimuli presented in quiet, the modulation gain at low frequencies of modulation (approx less than 50 Hz) was inversely proportional to the neuron's mean firing rate in response to both the modulated stimulus and to a pure tone at an equivalent level. In 43% of units the mean discharge rates in response to the AM stimuli were greatest for those modulation frequencies that generated the largest temporal responses. These discharge-rate maxima occurred at signal intensities corresponding to the steeply sloping part of the neuron's pure-tone rate-intensity function (RIF). The change in mean-rate response to modulated stimuli, as a function of intensity, was qualitatively similar to the pure-tone RIF. Adding broadband noise to the modulated stimulus increased the neuron's temporal response to low modulation frequencies. This increase in modulation gain was correlated with mean firing rate in response to the modulation but did not bear a simple relationship to the noise-induced shift in the RIF measured for a pure tone.

Acoustic Stimulation↗
PubMed1991

A comparison of steady-state evoked potentials to modulated tones in awake and sleeping humans.

Steady-state evoked potential responses were measured to binaural amplitude-modulated (AM) and combined amplitude- and frequency-modulated (AM/FM) tones. For awake subjects, AM/FM tones produced larger amplitude responses than did AM tones. Awake and sleeping responses to 30-dB HL AM/FM tones were compared. Response amplitudes were lower during sleep and the extent to which they differed from awake amplitudes was dependent on both carrier and modulation frequencies. Background EEG noise at the stimulus modulation frequency was also reduced during sleep and varied with modulation frequency. A detection efficiency function was used to indicate the modulation frequencies likely to be most suitable for electrical estimation of behavioral threshold. In awake subjects, for all carrier frequencies tested, detection efficiency was highest at a modulation frequency of 45 Hz. In sleeping subjects, the modulation frequency regions of highest efficiency varied with carrier frequency. For carrier frequencies of 250 Hz, 500 Hz, and 1 kHz, the highest efficiencies were found in two modulation frequency regions centered on 45 and 90 Hz. For 2 and 4 kHz, the highest efficiencies were at modulation frequencies above 70 Hz. Sleep stage affected both response amplitude and background EEG noise in a manner that depended on modulation frequency. The results of this study suggest that, for sleeping subjects, modulation frequencies above 70 Hz may be best when using steady-state potentials for hearing threshold estimation.

Acoustics↗
PubMed1994

Masking of speech by amplitude-modulated noise.

The masking of speech by amplitude-modulated and unmodulated speech-spectrum noise has been evaluated by the measurement of monaural speech recognition in such noise on young and elderly subjects with normal-hearing and elderly hearing-impaired subjects with and without a hearing aid. Sinusoidal modulation with frequencies covering the range 2-100 Hz, as well as an irregular modulation generated by the sum of four sinusoids in random phase relation, was used. Modulation degrees were 100%, +/- 6 dB, and +/- 12 dB. Root mean-square sound pressure level was equal for modulated and unmodulated maskers. For the normal-hearing subjects, essentially all types of modulated noise provided some release of speech masking as compared to unmodulated noise. Sinusoidal modulation provided more release of masking than the irregular modulation. The release of masking increased with modulation depth. It is proposed that the number and duration of low-level intervals are essential factors for the degree of masking. The release of masking was found to reach a maximum at a modulation frequency between 10 and 20 Hz for sinusoidal modulation. For elderly hearing-impaired subjects, the release of masking obtained from amplitude modulation was consistently smaller than in the normal-hearing groups, presumably related to changes in auditory temporal resolution caused by the hearing loss. The average speech-to-noise ratio required for 30% correct speech recognition varied greatly between the groups: For young normal-hearing subjects it was -15 dB, for elderly normal-hearing it was -9 dB, for elderly hearing-impaired subjects in the unaided listening condition it was +2 dB and in the aided condition it was +3 dB. The results support the conclusion that within the methodological context of the study, age as well as sensorineural hearing loss, as such, influence speech recognition in noise more than what can be explained by the loss of audibility, according to the audiogram and the masking noise spectrum.

Adolescent↗
PubMed1995

The synthetic-analytic listening task for modulated signals.

The synthetic-analytic listening task (SALT) developed by Dye and colleagues [Dye et al., J. Acoust. Soc. Am. 96, 2720-2731 (1994)] was applied to a task in which an amplitude-modulated tonal carrier was presented as a target during the standard stimulus. The standard stimulus was followed by a test stimulus in which the target along with another amplitude-modulated carrier (the distractor) was presented. The listener determined if in the test stimulus, the target (which was presented along with the distractor) was higher or lower in modulation depth than when the target was presented alone as the standard stimulus. The target and distractor were either 1- or 4-kHz carriers modulated at one of ten depths of modulation during the test stimulus at modulation rates ranging from 4 to 64 Hz. SALT was used to estimate the relative weight listeners assigned to the target and distractor as a function of the difference between their modulation rates, both for target carrier frequencies above and for target carrier frequencies below the distractor carrier frequency. When the target and distractor were modulated at the same rate, the target and distractor weights were equal, indicating synthetic listening. When the target and distractor differed in modulation rate, the listener gave more weight to the target suggesting a form of analytic listening. The result demonstrate the applicability of SALT to studies of modulation and reinforce the claim that different spectral components modulated with the same modulation pattern are processed synthetically.

Auditory Perception↗
PubMed1991

Modulation of synaptic transmission at Ia-afferent fiber connections on motoneurons during high-frequency stimulation: role of postsynaptic target.

1. High-frequency stimulation of single group Ia-fibers results in modulation of excitatory postsynaptic potential (EPSP) amplitude recorded in target motoneurons. This can be either positive (EPSP amplitude increases in response to successive stimuli in the high-frequency burst) or negative (decrease in EPSP amplitude). We have investigated whether the magnitude of modulation is associated with the stimulated afferent, the responding motoneuron, or the amplitude of the EPSP. 2. In agreement with previous findings, we found that positive modulation tends to occur at connections generating small EPSPs and negative modulation, at those producing large EPSPs. Because large EPSPs generally are evoked in motoneurons with low values of rheobase, we found, as anticipated, that connections on low rheobase motoneurons are prone to negative modulation during high-frequency stimulation, whereas those on high rheobase motoneurons (which tend to generate small EPSPs) are prone to positive modulation. 3. In experiments where the projection of multiple afferents to a single motoneuron was studied, we found that amplitude modulation was similar despite differences in EPSP amplitude. Thus in a given motoneuron there is no relationship between modulation and amplitude, in contrast to the existence of such a relationship in the population of connections as a whole. 4. In the converse experiments where the projection of single afferents to multiple motoneurons was studied, we found marked variability in the modulation patterns with clear indications that amplitude and modulation are correlated as in the entire population of Ia/motoneuron connections. 5. We tested the constancy of modulation patterns evoked in a given motoneuron by comparing the modulation patterns evoked in motoneurons by single fibers, and by stimulation of the heteronymous nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Cochlear nerve fiber responses to amplitude-modulated stimuli: variations with spontaneous rate and other response characteristics.

1. Single-fiber responses to sinusoidally amplitude-modulated (AM) tones were recorded from the cochlear nerves of anesthetized guinea pigs. Stimuli were presented at the fiber's characteristic frequency (CF) and covered the intensity range between the fiber's minimum rate threshold and 90-100 dB SPL in 5- or 6-dB steps. The amount of modulation in each fiber's response and the average rate of the responses were quantified. The observed response modulation was compared with the modulation to be expected on the assumption that the instantaneous discharge rates varied with intensity in the same way that the average rates did (i.e., as predicted from each fiber's average-rate vs. level function). 2. The difference between the observed and expected response modulation varied widely across fibers. In most fibers' the responses to a limited range of stimulus intensities (typically between 20 and 30 dB above the fiber's rate threshold) were modulated far more than expected on the basis of their average rates, with responses to stimuli either above or below this range differing progressively less from expectation. Little or no response modulation was observed above approximately 70 dB SPL in these fibers. Other fibers exhibited response modulation that exceeded the expected modulation by smaller amounts, but maintained this modulation to much higher sound pressure levels. 3. The discrepancy between the observed and expected responses to AM stimuli also varied with the frequency of modulation (fm) within individual fibers. The discrepancies were least pronounced at low fms (e.g., 10 Hz) but became progressively larger as fm was increased to between 50 and 320 Hz (subject to the inter-fiber variations described in 2, above). 4. The AM response characteristics varied systematically with the fiber's spontaneous rate and other response characteristics (e.g., rate threshold, CF rate vs. level function type, and rapid adaptation characteristics). In particular, the most sensitive, high spontaneous rate fibers had responses that adapted rapidly after the onset of a stimulus, and showed the greatest enhancement of AM-related information at low-to-moderate stimulus intensities. However, these fibers appeared incapable of encoding AM-related information at high intensities, since their response rates "saturated" and their AM response enhancements diminished around 30 dB above threshold. In contrast, the less sensitive (i.e., higher threshold), lower spontaneous rate fibers showed less evidence of rapid adaptation near the onsets of their response, and lesser enhancements of the modulated responses predicted from their average-rate versus level functions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗